MP83-03: Detection of urothelial carcinoma using selected ... ss hematuria: A prospective, single-center study

Detection of urothelial carcinoma using selected urine-DNA methylation biomarkers in patients with gross hematuria: A prospective, single-center study

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INTRODUCTION

Hematuria is the most common symptom of urothelial carcinomas (UC) but is often idiopathic. Cystoscopy is expensive which involves considerable patient discomfort, and conventional urine cytology for non-invasive UC detection and disease monitoring suffers from poor sensitivity. We aim to evaluate the performance of genes selected from a previous study in detecting UC in voided urine samples from patients with gross hematuria.

METHODS

Using methylation-sensitive PCR, we examined the promoter methylation status of ten genes in voided urine samples among 473 patients at our institution, including 217 UC patients and 256 control subjects.

RESULTS

The final combination of VIM, CDH1, SALL3, TMEFF2, RASSF1A, BRCA1, GDF15 and ABCC6 identified UC with a sensitivity of 0.83 and a specificity of 0.60. Additionally, a panel of selected genes (CDH1, HSPA2, RASSF1A, TMEFF2, VIM and GDF15) identified upper tract urinary carcinomas (UTUC) with 0.82 sensitivity and a specificity of 0.68. Remarkably, a different panel (CDH1, SALL3, THBS1, TMEFF2, VIM and GDF15) identified UC in patients with gross hematuria with 0.89 sensitivity and 0.74 specificity, and perfect sensitivity (0.91) and specificity (0.92) could be achieved when cytology was included. Limitations include the single method used to detect methylation status, further validation needed in a larger multicenter study and for patients after surgery.

CONCLUSION

The selected urine-DNA methylation biomarkers are reliable, non-invasive, and cost-effective diagnostic tools for bladder carcinoma and UTUC for patients with gross hematuria.

Funding: This work was supported by grants from the Collaborative Research Foundation of Peking University Health Science Center and National Taiwan University, College of Medicine (BMU20120318), the Natural Science Foundation of Beijing Municipality (7152146), the Clinical Features Research of Capital (No. Z151100004015173) and the Capital Health Research and Development Special Fund (2016-1-4077).